p28(GANK) associates with p300 to attenuate the acetylation of RelA.

Abstract:

:Oncoprotein p28(GANK), overexpressed in hepatocellular carcinomas (HCC), binds to RelA and retains NF-κB in the cytoplasm to suppress NF-κB transactivation. However, the mechanism has not yet been elucidated. In this study, we clarified the mechanism of NF-κB regulated by p28(GANK). p28(GANK) reduced TNF-α-induced nuclear translocation of RelA/NF-κB independent of HDAC3. p28(GANK) interacted with p300 to attenuate assembly of RelA with p300, which lessened acetylation of RelA on the lysine 310 sites. Moreover, overexpression of p28(GANK) attenuated the capability of NF-κB binding to the target gene IκBα promoter, but also weakened adriamycin-induced NF-κB pro-apoptotic gene Fas and FasL expression, which subsequently made p53-deficient tumor cells resistance to adriamycin. These results present mechanistic insight into the key role of p28(GANK) in post-translational regulation of RelA/NF-κB.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Ren YB,Luo T,Li J,Fu J,Wang Q,Cao GW,Chen Y,Wang HY

doi

10.1002/mc.22235

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

1626-35

issue

12

eissn

0899-1987

issn

1098-2744

journal_volume

54

pub_type

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